Randomised, cross-over, comparative bioavailability trial of matrix type transdermal drug delivery system (TDDS) of carvedilol and hydrochlorothiazide combination in healthy human volunteers: a pilot study.

ABSTRACT

The present study deals with transdermal drug delivery system (TDDS) of Carvedilol (CRV) and Hydrochlorothiazide (HCTZ). It compares the bioavailability of these two study drugs from a TDDS with conventional immediate release oral tablets in healthy volunteers. The TDDS was also evaluated for any adverse drug reaction. This was an open-label, randomised, single centre, two-treatment, two period, single dose, crossover pilot study of two formulations of cardiovascular agents. Subjects (n=10) were randomised to have a TDDS applied to their abdominal skin for 72h or receive one oral tablet each of CRV and HCTZ respectively in period I, followed by 1-week washout period. They received the alternative treatment in period II. A significant improvement in bioavailability was observed with the transdermal patches over oral tablets as observed by the mean AUC((0)(-)(t)) values 4004.37+/-180.98 and 1824.30+/-17.43ngh/mL respectively for CRV and HCTZ as compared to 753.46+/-53.34 and 392.89+/-34.23ngh/mL respectively, with the oral tablets. The TDDS possesses significant potential for skin irritation. The TDDS developed in our laboratory produced therapeutically effective plasma concentrations of the cardiovascular agents up to a range of 60 to 72h (in different volunteers with a mean=66h). It could be concluded from these observations that the TDDS meets the intended goal of at least 2day management of stage II hypertension with application of a single transdermal patch, hence improving patient compliance over the inconvenience seen with frequent oral administration.